In vitro testing methods such as dissolution testing are useful for simulating the conditions under which a substance such as a pharmaceutical formulation is released under controlled conditions into a physiological environment such as a gastrointestinal or vascular environment. The releasing of a sample formulation into appropriate media such as by dissolution facilitates the acquisition of optical signals or other data from which concentration, release rate or other information can be derived for prediction of or correlation with actual, in vivo conditions. Some techniques entail agitation of the sample in media such as by stirring, rotation, or reciprocation.
For example, Chapters 711 (Dissolution) and 724 (Extended Release) of the United States Pharmacopoeia (USP) guidelines describe the use of several techniques for performing agitation in test vessels containing a dissolution medium that is usually temperature-regulated. These techniques include the use of a rotating basket (Apparatus 1), a rotating paddle (Apparatus 2), a reciprocating cylinder (Apparatus 3), and a reciprocating holder (Apparatus 7). Each apparatus requires the insertion of a motor-powered shaft into the test vessel. In Apparatus 1, a stainless steel basket with mesh sides is provided to contain a tablet, capsule or other dosage form and is rotated by a stainless steel shaft. In Apparatus 2, a rotating paddle is formed from a blade and shaft. In Apparatus 3, a glass reciprocating cylinder with open, mesh-covered ends is provided to contain a dosage form. The reciprocating cylinder is vertically raised and lowered in a vessel at a prescribed dip rate. The top of the reciprocating cylinder has a perforated cover that is attached to a shaft. An evaporation cap is fitted over the reciprocating cylinder and the container. This cap, however, has air holes and the shaft required for reciprocation extends through the cap. Hence, the cap cannot fully seal the interior of the container, and an unacceptable loss of solution by evaporation can result. A similar apparatus is described in U.S. Pat. No. 5,011,662. Similarly, in Apparatus 7, other types of sample holders attached to shafts, such as nylon net bags, CUPROPHAN® material, stainless steel coils, TEFLON® disks, and TEFLON® cylinders, are vertically reciprocated in vessels for the testing of dosage forms such as tablets and transdermal patches.
As noted, all such systems have historically required the use of a shaft that must be extended into the media container in order to be able to reciprocate, rotate or stir the sample through the media and thereafter removed. Accordingly, a significant amount of evaporation loss often cannot be avoided in these systems. Evaporation loss can reduce the effectiveness of testing procedures entailing agitation. Moreover, shafts are prone to wobble or become misaligned and hence frequently require recalibration or replacement. In addition, the containers employed to hold media have traditionally been sized to accommodate the largest type of sample or sample holder to be tested. In this manner, the same-sized container can be employed in the testing of a wide range of differently sized samples and sample holders. However, when testing relatively small samples, the standardized container size provides an excessively large volume of media through which the sample is reciprocated. As a result, the resolution of data acquired during testing is not optimized for many kinds of samples. Furthermore, conventional testing methods and apparatus are not specifically designed for handling, supporting, and testing newer types of pharmaceutical delivery means such as stents and other carriers of analytical material.
Therefore, a need exists for an apparatus and method for agitating a sample in a container while preventing—i.e., substantially reducing or eliminating—the loss of contents of the container via evaporation or other mechanisms. A need also exists for an apparatus and method for agitating a sample in a container without the requirement of a shaft extending into the container from the ambient environment. A need further exists for an apparatus and method for agitating a sample in a container in which the volume of the container is better tailored to the size of the sample, the sample holder, and/or other items residing in the container. A need further exists for an apparatus and method for handling, supporting, and testing certain types of carriers of drug compounds or other analytical materials.